Molecular characterization of Novel ATM fusions in chronic lymphocytic leukemia and T-cell prolymphocytic leukemia

Rashmi Kanagal-Shamanna, Haiyan Bao, Hutton Kearney, Stephanie Smoley, Zhenya Tang, Rajyalakshmi Luthra, Hui Yang, Shanshan Zhang, Pei Lin, Depei Wu, L. Jeffrey Medeiros, Xinyan Lu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


ATM deletions and/or mutations are recurrent in lymphoid neoplasms while rearrangements are rare. In this study, we used mate pair sequencing (MPseq) technology to characterize two novel ATM rearrangements in one patient with chronic lymphocytic leukemia (CLL) and one patient with T-prolymphocytic leukemia (T-PLL). Both patients showed chromosome 11q22 aberrations encompassing ATM by conventional karyotype and fluorescence in situ hybridization: isolated t(11;13)(q22;q14) in CLL and a complex karyotype with apparent 11q deletion and unbalanced der(14)t(11;14)(q22;p11.2) in T-PLL. MPseq identified ATM-LINC00371 fusion in CLL and ATM-USP28 in T-PLL, both of which led to ATM inactivation, confirmed by loss of immunohistochemical protein expression. Next-generation sequencing mutation analysis detected concurrent ATM mutation(s) CLL patient, while T-PLL lacked ATM mutation. ATM rearrangements, not apparently detectable using standard laboratory technologies, represent another mechanism of loss-of-function. Recent high-throughput technologies such as MPseq can uncover novel pathogenic gene fusions and resolve complex chromosomal rearrangements in hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)865-875
Number of pages11
JournalLeukemia and Lymphoma
Issue number4
StatePublished - 2022


  • ATM fusion
  • ATM rearrangement
  • CLL
  • MPseq
  • T-PLL
  • mate-pair sequencing

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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